Semaglutide targets muscle mitochondria to regulate osteoarthritis

ABSTRACT:

Metabolic and inflammatory diseases often coexist, and become important challenges facing global health, and obesity has shown to be a susceptibility factor for osteoarthritis (OA). As a metabolic regulatory drug for lowering blood sugar and body weight, semaglutide has shown additional therapeutic effects in OA, but the underlying mechanism requires further investigation. Here we employed cross-tissue single-cell RNA sequencing (scRNA-seq) analysis, and found that semaglutide significantly improved metabolic disorders in muscle tissue under high-fat diet (HFD) and OA conditions in mice. The results of scRNA-seq and mitochondrial proteomics indicated that semaglutide targeted muscle mitochondria to regulate glutamate metabolism during OA. Intriguingly, intramuscular injection of semaglutide pre-stimulated mitochondria from muscle stem cell could significantly alleviate OA inflammation and pain symptoms. These findings reveal the mitochondrial regulatory mechanism in the muscle-OA axis, and provide a new perspective for the application of semaglutide in OA treatment.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse-phase, Liquid Chromatography MS - positive - reverse-phase

PROVIDER: MTBLS14059 | MetaboLights | 2026-05-06

REPOSITORIES: MetaboLights